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(Circulation Research. 2003;92:1225.)
© 2003 American Heart Association, Inc.

Cellular Biology

Hypercapnic Acidosis Activates K_ATP Channels in Vascular Smooth Muscles

Xueren Wang, Jianping Wu, Li Li, Fuxue Chen, Runping Wang, Chun Jiang

From the Department of Biology, Georgia State University, Atlanta, Ga.

Correspondence to Chun Jiang, Department of Biology, Georgia State University, 24 Peachtree Center Ave, Atlanta, GA 30302-4010. E-mail cjiang{at}gsu.edu

ATP-sensitive K⁺ channels (K_ATP) couple intermediary metabolism to cellular activity, and may play a role in the autoregulation of vascular tones. Such a regulation requires cellular mechanisms for sensing O₂, CO₂, and pH. Our recent studies have shown that the pancreatic K_ATP isoform (Kir6.2/SUR1) is regulated by CO₂/pH. To identify the vascular K_ATP isoform(s) and elucidate its response to hypercapnic acidosis, we performed these studies on vascular smooth myocytes (VSMs). Whole-cell and single-channel currents were studied on VSMs acutely dissociated from mesenteric arteries and HEK293 cells expressing Kir6.1/SUR2B. Hypercapnic acidosis activated an inward rectifier current that was K⁺-selective and sensitive to levcromakalim and glibenclamide with unitary conductance of 35pS. The maximal activation occurred at pH 6.5 to 6.8, and the current was inhibited at pH 6.2 to 5.9. The cloned Kir6.1/SUR2B channel responded to hypercapnia and intracellular acidification in an almost identical pattern to the VSM current. In situ hybridization histochemistry revealed expression of Kir6.1/SUR2B mRNAs in mesenteric arteries. Hypercapnia produced vasodilation of the isolated and perfused mesenteric arteries. Pharmacological interference of the K_ATP channels greatly eliminated the hypercapnic vasodilation. These results thus indicate that the Kir6.1/SUR2B channel is a critical player in the regulation of vascular tones during hypercapnic acidosis.

Key Words: K_ATP • Kir6.1 • hypercapnia • ATP • vasodilation

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